Department of Respiratory Medicine, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
Metabolism. 2011 Jul;60(7):957-64. doi: 10.1016/j.metabol.2010.09.004. Epub 2010 Nov 5.
Skeletal muscle biopsy studies have consistently shown a decreased oxidative phenotype in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Limited information is available regarding potential adaptations or abnormalities in anaerobic metabolism and glucose homeostasis. Whole-body glucose production was assessed at rest and during exercise in COPD patients with moderate disease severity (forced expiratory volume in 1 second, 52% ± 3%), prestratified into normal-weight (n = 7; body mass index [BMI], 27.5 ± 0.9 kg·m(-2)) and underweight subjects (n = 6; BMI, 20.6 ± 0.7 kg·m(-2)), and in 8 healthy controls matched for age and BMI with the normal-weight COPD group. Glucose tolerance was normal in all subjects. Rate of appearance (R(a)) of glucose at rest and during submaximal cycling exercise was measured in postabsorptive state by infusion of stable isotope tracer [6,6-(2)H(2)]glucose. Resting glucose R(a) was significantly enhanced in underweight COPD patients compared with controls (16.7 ± 0.3 vs 15.1 ± 0.4 μmol·kg fat-free mass(-1)·min(-1), P < .05) and was inversely related to fat-free mass (r = -0.75, P < .01). Furthermore, the exercise-induced increase in glucose R(a) was enhanced in COPD patients (81.9% ± 3.4% vs 72.1% ± 2.0%, P = .05), resulting in elevated end-of-exercise glucose output. Differences were most pronounced in underweight patients, who were also characterized by enhanced plasma catecholamine levels and decreased insulin concentrations (all, P < .05). In normal-weight patients, there was evidence for decreased insulin sensitivity assessed by homeostatic modeling technique. Whole-body glucose production is increased in underweight COPD patients with normal glucose tolerance. It is hypothesized that lowered body weight in COPD has unique effects on glucose uptake despite reduced skeletal muscle oxidative capacity, relative hypoxemia, and sympathetic activation.
骨骼肌活检研究表明，中重度慢性阻塞性肺疾病（COPD）患者的氧化表型降低。关于无氧代谢和葡萄糖稳态的潜在适应或异常的信息有限。在中重度疾病严重程度（第 1 秒用力呼气量，52%±3%）的 COPD 患者中，评估了静息和运动时的全身葡萄糖产生，这些患者根据体重指数（BMI）分为正常体重（n=7；BMI，27.5±0.9kg·m(-2))和体重不足（n=6；BMI，20.6±0.7kg·m(-2))，并与正常体重的 COPD 组匹配了 8 名年龄和 BMI 匹配的健康对照者。所有受试者的葡萄糖耐量均正常。在吸收后状态下，通过输注稳定同位素示踪剂[6,6-(2)H(2)]葡萄糖，测量静息和亚最大自行车运动时葡萄糖的出现率（R(a)）。与对照组相比，体重不足的 COPD 患者的静息时葡萄糖 R(a)显著增加（16.7±0.3 对 15.1±0.4μmol·kg 去脂体重(-1)·min(-1)，P<.05），并且与去脂体重呈负相关（r=-0.75，P<.01）。此外，COPD 患者的葡萄糖 R(a)的运动诱导增加增强（81.9%±3.4%对 72.1%±2.0%，P=.05），导致运动结束时的葡萄糖输出增加。在体重不足的患者中，差异最为明显，这些患者的血浆儿茶酚胺水平升高，胰岛素浓度降低（均 P<.05）。在正常体重的患者中，通过稳态模型技术评估存在胰岛素敏感性降低的证据。在糖耐量正常的体重不足的 COPD 患者中，全身葡萄糖生成增加。据推测，尽管骨骼肌氧化能力降低、相对低氧血症和交感神经激活，COPD 患者的体重降低对葡萄糖摄取具有独特的影响。
